Linked Life Data

11290783

Source:http://linkedlifedata.com/resource/pubmed/id/11290783

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-4-6
pubmed:abstractText
The chemokine stroma-derived factor (SDF)-1, and its receptor, CXCR-4, have been shown to be essential for the translocation of hemopoietic stem cells from the fetal liver to the bone marrow (BM). We hypothesized that if CXCR-4 plays a crucial role in the localization of human hemopoiesis, stem cells from distinct tissue sources should demonstrate distinct CXCR-4 expression or signaling profiles. CD34(+) cells from BM were compared with blood: either mobilized peripheral blood or umbilical cord blood. Unexpectedly, significantly higher levels of CXCR-4 surface expression on CD34(+) cells from blood sources, mobilized peripheral blood, or cord blood were observed compared with BM (p = 0.0005 and p = 0.002, respectively). However, despite lower levels of CXCR-4, responsiveness of the cells to SDF-1 as measured by either calcium flux or transmigration was proportionally greatest in cells derived from BM. Further, internalization of CXCR-4 in response to ligand, associated with receptor desensitization, was significantly lower on BM-derived cells. Therefore, preserved chemokine receptor signaling was highly associated with marrow rather than blood localization. To test the functional effects of perturbing CXCR-4 signaling, adult mice were exposed to the methionine-SDF-1beta analog that induces prolonged down-regulation/desensitization of CXCR-4 and observed mobilization of Lin(-), Sca-1(+), Thy-1(low), and c-kit(+) hemopoietic progenitor cells to the peripheral blood with a >30-fold increase compared with PBS control (p = 0.0007 day 1 and p = 0.004 day 2). These data demonstrate that CXCR-4 expression and function can be dissociated in progenitor cells and that desensitization of CXCR-4 induces stem cell entry into the circulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5027-33
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11290783-Adult, pubmed-meshheading:11290783-Animals, pubmed-meshheading:11290783-Bone Marrow Cells, pubmed-meshheading:11290783-Calcium, pubmed-meshheading:11290783-Cell Membrane, pubmed-meshheading:11290783-Cell Movement, pubmed-meshheading:11290783-Chemokine CXCL12, pubmed-meshheading:11290783-Chemokines, CXC, pubmed-meshheading:11290783-Chemotaxis, Leukocyte, pubmed-meshheading:11290783-Cytokines, pubmed-meshheading:11290783-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:11290783-Hematopoietic Stem Cell Mobilization, pubmed-meshheading:11290783-Hematopoietic Stem Cells, pubmed-meshheading:11290783-Humans, pubmed-meshheading:11290783-Intracellular Fluid, pubmed-meshheading:11290783-Ligands, pubmed-meshheading:11290783-Mice, pubmed-meshheading:11290783-Mice, Inbred Strains, pubmed-meshheading:11290783-Organ Specificity, pubmed-meshheading:11290783-Receptors, CXCR4, pubmed-meshheading:11290783-Signal Transduction
pubmed:year
2001
pubmed:articleTitle
CXCR-4 desensitization is associated with tissue localization of hemopoietic progenitor cells.
pubmed:affiliation
AIDS Research Center, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't